TUBA8

Chr 22AD

tubulin alpha 8

Also known as: CDCBM8, MACTHC2, TUBAL2

NCBI Gene: 51807ENSG00000183785UniProt: Q9NY65

This gene encodes a member of the alpha tubulin protein family. Alpha tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene are associated with polymicrogyria and optic nerve hypoplasia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Primary Disease Associations & Inheritance

Macrothrombocytopenia, isolated, 2, autosomal dominantMIM #619840
AD
464
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TUBA8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 223 VUS of 464 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.09LOEUF
pLI 0.000
Z-score 1.31
OE 0.63 (0.38–1.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.89 (0.81–0.99)
250 obs / 279.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.63 (0.38–1.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 9 / 14.3Missense obs/exp: 250 / 279.7Syn Z: 0.16

ClinVar Variant Classifications

464 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic1
VUS223
Likely Benign142
Benign20
Conflicting4
70
Pathogenic
1
Likely Pathogenic
223
VUS
142
Likely Benign
20
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
69
0
70
Likely Pathogenic
0
0
1
0
1
VUS
14
187
21
1
223
Likely Benign
0
3
41
98
142
Benign
0
2
15
3
20
Conflicting
—4
Total14193147102460

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TUBA8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TUBA8-related polymicrogyria with optic nerve hypoplasia

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUBULIN, ALPHA-8; TUBA8
MIM #605742 · *

Macrothrombocytopenia, isolated, 2, autosomal dominant

MIM #619840

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive transcriptome analysis and lncRNA-miRNA-mRNA establishment of schizophrenia based on induced pluripotent stem cells.
Jia N et al.·Schizophr Res
2025
Mutations in α- and β-tubulin encoding genes: implications in brain malformations.
Romaniello R et al.·Brain Dev
2015Review
The wide spectrum of tubulinopathies: what are the key features for the diagnosis?
Bahi-Buisson N et al.·Brain
2014
Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations.
Tischfield MA et al.·Curr Opin Genet Dev
2011Review
Radiation hybrid mapping of 18 positional and physiological candidate genes for arthrogryposis multiplex congenita on porcine chromosome 5.
Genini S et al.·Anim Genet
2006
Mutation of the variant alpha-tubulin TUBA8 results in polymicrogyria with optic nerve hypoplasia.
Abdollahi MR et al.·Am J Hum Genet
2009
Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome.
Eguchi M et al.·Am J Med Genet A
2018Review
Clinical Implementation of Targeted Gene Sequencing for Malformation of Cortical Development.
Lee S et al.·Pediatr Neurol
2020
Analysis of 17 genes detects mutations in 81% of 811 patients with lissencephaly.
Di Donato N et al.·Genet Med
2018Cohort
Downregulation of genes outside the deleted region in individuals with 22q11.2 deletion syndrome.
Dantas AG et al.·Hum Genet
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools